tbuckley/cabot-search huggingface dataset:
The Type I Interferon Signature Reflects Multiple Phenotypic and Activity Measures in Dermatomyositis
Authors: Mika M. Tabata, Luqman Mushila Hodgkinson, Tiffany T. Wu, Shufeng Li, Christine Huard, Shanrong Zhao, Donald Bennett, Jillian Johnson, Cassandra Tierney, Wen He, Janet E. Buhlmann, Karen M. Page, Kristen Johnson, Livia Casciola‐Rosen, Lorinda Chung, Kavita Y. Sarin, David Fiorentino
Journal: Arthritis & Rheumatology (2023)

The type 1 interferon (IFN) pathway is up-regulated in dermatomyositis (DM). We sought to define how organ-specific disease activity as well as autoantibodies and other clinical factors are independently associated with systemic type I IFN activity in adult patients with DM.RNA sequencing was performed on 355 whole blood samples collected from 202 well-phenotyped DM patients followed up during the course of their clinical care. A previously defined 13-gene type I IFN score was modeled as a function of demographic, serologic, and clinical variables using both cross-sectional and longitudinal data.The pattern of type I IFN-driven transcriptional response was stereotyped across samples with a sequential modular activation pattern strikingly similar to systemic lupus erythematosus. The median type I IFN score was higher or lower in patients with anti-melanoma differentiation-associated protein 5 (anti-MDA-5) or anti-Mi-2 antibodies, respectively, compared to patients without these antibodies. Absolute type I IFN score was independently associated with muscle and skin disease activity, interstitial lung disease, and anti-MDA-5 antibodies. Changes in the type I IFN score over time were significantly associated with changes in skin or muscle disease activity. Stratified analysis accounting for heterogeneity in organ involvement and antibody class revealed high correlation between changes in the type I IFN score and skin disease activity (Spearman's ρ = 0.84-0.95).The type I IFN score is independently associated with skin and muscle disease activity as well as certain clinical and serologic features in DM. Accounting for the effect of muscle disease and anti-MDA-5 status revealed that the type I IFN score is strongly correlated with skin disease activity, providing support for type I IFN blockade as a therapeutic strategy for DM.
Author Correction: Enhancing attention in children using an integrated cognitive-physical videogame: A pilot study
Authors: J. A. Anguera, M. A. Rowe, J. J. Volponi, M. Elkurdi, B. Jurigova, A. J. Simon, R. Anguera-Singla, C. L. Gallen, A. Gazzaley, E. J. Marco
Journal: npj Digital Medicine (2023)
Microbial metabolites in colorectal tumorigenesis and cancer therapy
Authors: Yali Liu, Harry Cheuk-Hay Lau, Jun Yu
Journal: Gut Microbes (2023)

Trillions of microbes are indigenous to the human gastrointestinal tract, together forming an ecological community known as the gut microbiota. The gut microbiota is involved in dietary digestion to produce various metabolites. In healthy condition, microbial metabolites have unneglectable roles in regulating host physiology and intestinal homeostasis. However, increasing studies have reported the correlation between metabolites and the development of colorectal cancer (CRC), with the identification of oncometabolites. Meanwhile, metabolites can also influence the efficacy of cancer treatments. In this review, metabolites derived from microbes-mediated metabolism of dietary carbohydrates, proteins, and cholesterol, are introduced. The roles of pro-tumorigenic (secondary bile acids and polyamines) and anti-tumorigenic (short-chain fatty acids and indole derivatives) metabolites in CRC development are then discussed. The impacts of metabolites on chemotherapy and immunotherapy are further elucidated. Collectively, given the importance of microbial metabolites in CRC, therapeutic approaches that target metabolites may be promising to improve patient outcome.
Allogenic and autologous anti-CD7 CAR-T cell therapies in relapsed or refractory T-cell malignancies
Authors: Yinqiang Zhang, Chenggong Li, Mengyi Du, Huiwen Jiang, Wenjing Luo, Lu Tang, Yun Kang, Jia Xu, Zhuolin Wu, Xindi Wang, Zhongpei Huang, Yanlei Zhang, Di Wu, Alex H. Chang, Yu Hu, Heng Mei
Journal: Blood Cancer Journal (2023)

Abstract Chimeric antigen receptor-T (CAR-T) therapy remains to be investigated in T-cell malignancies. CD7 is an ideal target for T-cell malignancies but is also expressed on normal T cells, which may cause CAR-T cell fratricide. Donor-derived anti-CD7 CAR-T cells using endoplasmic reticulum retention have shown efficacy in patients with T-cell acute lymphoblastic leukemia (ALL). Here we launched a phase I trial to explore differences between autologous and allogeneic anti-CD7 CAR-T therapies in T-cell ALL and lymphoma. Ten patients were treated and 5 received autologous CAR-T therapies. No dose-limiting toxicity or neurotoxicity was observed. Grade 1–2 cytokine release syndrome occurred in 7 patients, and grade 3 in 1 patient. Grade 1–2 graft-versus-host diseases were observed in 2 patients. Seven patients had bone marrow infiltration, and 100% of them achieved complete remission with negative minimal residual disease within one month. Two-fifths of patients achieved extramedullary or extranodular remission. The median follow-up was 6 (range, 2.7–14) months and bridging transplantation was not administrated. Patients treated with allogeneic CAR-T cells had higher remission rate, less recurrence and more durable CAR-T survival than those receiving autologous products. Allogeneic CAR-T cells appeared to be a better option for patients with T-cell malignancies.
Transformation and survival in marginal zone lymphoma: a Finnish nationwide population-based study
Authors: Ilja Kalashnikov, Tomas Tanskanen, Leevi Viisanen, Nea Malila, Sirkku Jyrkkiö, Sirpa Leppä
Journal: Blood Cancer Journal (2023)

Marginal zone lymphoma (MZL) is an indolent B-cell malignancy with heterogeneous anatomical and clinical presentation. While MZLs are generally associated with long survival, some patients experience histological transformation to aggressive large B-cell lymphoma. Population-based long-term data on the transformation of MZL is limited. We conducted a nationwide population-based study to estimate the risk of transformation and relative survival in patients diagnosed with MZL in Finland from 1995-2018. We identified a total of 1454 patients with MZL from the Finnish Cancer Registry (FCR). The cumulative incidence of transformation was 4.7% (95% CI, 3.6-6.2) at 10 years. The highest incidence of transformation was observed in the patients with splenic MZL (14.0%; 95% CI, 8.6-22.7). The transformation was associated with a substantially increased risk of death (HR, 5.18; 95% CI, 3.58-7.50). Ten-year relative survival was 79% (95% CI, 73‒83%). Transformation, nodal MZL subtype, and older age at diagnosis were associated with increased excess mortality, whereas patients diagnosed at a later calendar period had a lower excess risk of death. We conclude that transformation resulted in a substantially increased mortality irrespective of MZL subtype compared with the patients without transformation. Our results also suggest a reduction in excess mortality in recent years.
Culture-expanded mesenchymal stromal cell therapy: does it work in knee osteoarthritis? A pathway to clinical success
Authors: Griffin Copp, Kevin P. Robb, Sowmya Viswanathan
Journal: Cellular and Molecular Immunology (2023)

Abstract Osteoarthritis (OA) is a degenerative multifactorial disease with concomitant structural, inflammatory, and metabolic changes that fluctuate in a temporal and patient-specific manner. This complexity has contributed to refractory responses to various treatments. MSCs have shown promise as multimodal therapeutics in mitigating OA symptoms and disease progression. Here, we evaluated 15 randomized controlled clinical trials (RCTs) and 11 nonrandomized RCTs using culture-expanded MSCs in the treatment of knee OA, and we found net positive effects of MSCs on mitigating pain and symptoms (improving function in 12/15 RCTs relative to baseline and in 11/15 RCTs relative to control groups at study endpoints) and on cartilage protection and/or repair (18/21 clinical studies). We examined MSC dose, tissue of origin, and autologous vs. allogeneic origins as well as patient clinical phenotype, endotype, age, sex and level of OA severity as key parameters in parsing MSC clinical effectiveness. The relatively small sample size of 610 patients limited the drawing of definitive conclusions. Nonetheless, we noted trends toward moderate to higher doses of MSCs in select OA patient clinical phenotypes mitigating pain and leading to structural improvements or cartilage preservation. Evidence from preclinical studies is supportive of MSC anti-inflammatory and immunomodulatory effects, but additional investigations on immunomodulatory, chondroprotective and other clinical mechanisms of action are needed. We hypothesize that MSC basal immunomodulatory “fitness” correlates with OA treatment efficacy, but this hypothesis needs to be validated in future studies. We conclude with a roadmap articulating the need to match an OA patient subset defined by molecular endotype and clinical phenotype with basally immunomodulatory “fit” or engineered-to-be-fit-for-OA MSCs in well-designed, data-intensive clinical trials to advance the field.
In situ forming injectable MSC-loaded GelMA hydrogels combined with PD for vascularized sweat gland regeneration
Authors: Enhe Jirigala, Bin Yao, Zhao Li, Yi-Jie Zhang, Chao Zhang, Li-Ting Liang, Fan-Liang Zhang, Xing-Yu Yuan, Xian-Lan Duan, Wei Song, Meng-De Zhang, Yi Kong, Xiao-Bing Fu, Sha Huang
Journal: Military Medical Research (2023)
Down-regulation of DNA key protein-FEN1 inhibits OSCC growth by affecting immunosuppressive phenotypes via IFN-γ/JAK/STAT-1
Authors: Shimeng Wang, Xiangjian Wang, Jun Sun, Jin Yang, Deyang Wu, Fanglong Wu, Hongmei Zhou
Journal: International Journal of Oral Science (2023)

Abstract Oral squamous cell carcinoma (OSCC) escape from the immune system is mediated through several immunosuppressive phenotypes that are critical to the initiation and progression of tumors. As a hallmark of cancer, DNA damage repair is closely related to changes in the immunophenotypes of tumor cells. Although flap endonuclease-1 (FEN1), a pivotal DNA-related enzyme is involved in DNA base excision repair to maintain the stability of the cell genome, the correlation between FEN1 and tumor immunity has been unexplored. In the current study, by analyzing the clinicopathological characteristics of FEN1, we demonstrated that FEN1 overexpressed and that an inhibitory immune microenvironment was established in OSCC. In addition, we found that downregulating FEN1 inhibited the growth of OSCC tumors. In vitro studies provided evidence that FEN1 knockdown inhibited the biological behaviors of OSCC and caused DNA damage. Performing multiplex immunohistochemistry (mIHC), we directly observed that the acquisition of critical immunosuppressive phenotypes was correlated with the expression of FEN1. More importantly, FEN1 directly or indirectly regulated two typical immunosuppressive phenotype-related proteins human leukocyte antigen (HLA-DR) and programmed death receptor ligand 1 (PD-L1), through the interferon-gamma (IFN-γ)/janus kinase (JAK)/signal transducer and activator transcription 1 (STAT1) pathway. Our study highlights a new perspective on FEN1 action for the first time, providing theoretical evidence that it may be a potential immunotherapy target for OSCC.
<scp>Lysosome‐Associated</scp> Membrane Protein 3 Induces <scp>Lysosome‐Dependent</scp> Cell Death by Impairing Autophagic Caspase 8 Degradation in the Salivary Glands of Individuals With Sjögren's Disease
Authors: Hiroyuki Nakamura, Tsutomu Tanaka, Changyu Zheng, Sandra A. Afione, Blake M. Warner, Masayuki Noguchi, Tatsuya Atsumi, John A. Chiorini
Journal: Arthritis & Rheumatology (2023)

Lysosome-associated membrane protein 3 (LAMP3) overexpression is implicated in the development and progression of Sjögren's disease (SjD) by inducing lysosomal membrane permeabilization (LMP) and apoptotic cell death in salivary gland epithelium. The aim of this study was to clarify the molecular details of LAMP3-induced lysosome-dependent cell death and to test lysosomal biogenesis as a therapeutic intervention.
Alcohol Consumption and Risk of Total Hip Replacement Due to Hip Osteoarthritis in Women
Authors: Nathalie E. Marchand, Yang Hu, Mingyang Song, Bernard A. Rosner, Elizabeth W. Karlson, Charles Ratzlaff, Bing Lu, Matthew H. Liang, Walter C. Willett
Journal: Arthritis & Rheumatology (2023)

This study was undertaken to examine the relationship between alcohol consumption and hip osteoarthritis in women. Alcohol has been associated with both adverse and beneficial health effects generally; however, the relationship between alcohol consumption and hip osteoarthritis has been minimally studied.
Lowering of Circulating Sclerostin May Increase Risk of Atherosclerosis and Its Risk Factors: Evidence From a <scp>Genome‐Wide</scp> Association <scp>Meta‐Analysis</scp> Followed by Mendelian Randomization
Authors: Jie Zheng, Eleanor Wheeler, Maik Pietzner, Till F. M. Andlauer, Michelle S. Yau, April E. Hartley, Ben Michael Brumpton, Humaira Rasheed, John P. Kemp, Monika Frysz, Jamie Robinson, Sjur Reppe, Vid Prijatelj, Kaare M. Gautvik, Louise Falk, Winfried Maerz, Ingrid Gergei, Patricia A. Peyser, Maryam Kavousi, Paul S. de Vries, Clint L. Miller, Maxime Bos, Sander W. van der Laan, Rajeev Malhotra, Markus Herrmann, Hubert Scharnagl, Marcus Kleber, George Dedoussis, Eleftheria Zeggini, Maria Nethander, Claes Ohlsson, Mattias Lorentzon, Nick Wareham, Claudia Langenberg, Michael V. Holmes, George Davey Smith, Jonathan H. Tobias
Journal: Arthritis & Rheumatology (2023)

In this study, we aimed to establish the causal effects of lowering sclerostin, target of the antiosteoporosis drug romosozumab, on atherosclerosis and its risk factors.
Clinical Images: Multiple punched‐out ulcerations on the abdomen in anti–melanoma differentiation–associated gene 5 dermatomyositis
Authors: Tomoyuki Mutoh, Mamoru Narita, Taichi Nagai, Sadanori Furudate, Shinji Taniuchi, Masataka Kudo, Hiroshi Fujii
Journal: Arthritis & Rheumatology (2023)

Disclosure form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Cell Type–Specific Biomarkers of Systemic Sclerosis Disease Severity Capture <scp>Cell‐Intrinsic</scp> and <scp>Cell‐Extrinsic</scp> Circuits
Authors: Jacob S. Berkowitz, Tracy Tabib, Hanxi Xiao, Gabrielle M. Sadej, Dinesh Khanna, Patrizia Fuschiotti, Robert A. Lafyatis, Jishnu Das
Journal: Arthritis & Rheumatology (2023)

Systemic sclerosis (SSc) is a multifactorial autoimmune fibrotic disorder involving complex rewiring of cell-intrinsic and cell-extrinsic signaling coexpression networks involving a range of cell types. However, the rewired circuits as well as corresponding cell-cell interactions remain poorly understood. To address this, we used a predictive machine learning framework to analyze single-cell RNA-sequencing data from 24 SSc patients across the severity spectrum as quantified by the modified Rodnan skin score (MRSS).
The critical role of apoptosis in mesenchymal stromal cell therapeutics and implications in homeostasis and normal tissue repair
Authors: Chiara Giacomini, Cecilia Granéli, Ryan Hicks, Francesco Dazzi
Journal: Cellular and Molecular Immunology (2023)

Abstract Mesenchymal stromal cells (MSCs) have been extensively tested for the treatment of numerous clinical conditions and have demonstrated good safety but mixed efficacy. Although this outcome can be attributed in part to the heterogeneity of cell preparations, the lack of mechanistic understanding and tools to establish cell pharmacokinetics and pharmacodynamics, as well as the poorly defined criteria for patient stratification, have hampered the design of informative clinical trials. We and others have demonstrated that MSCs can rapidly undergo apoptosis after their infusion. Apoptotic MSCs are phagocytosed by monocytes/macrophages that are then reprogrammed to become anti-inflammatory cells. MSC apoptosis occurs when the cells are injected into patients who harbor activated cytotoxic T or NK cells. Therefore, the activation state of cytotoxic T or NK cells can be used as a biomarker to predict clinical responses to MSC treatment. Building on a large body of preexisting data, an alternative view on the mechanism of MSCs is that an inflammation-dependent MSC secretome is largely responsible for their immunomodulatory activity. We will discuss how these different mechanisms can coexist and are instructed by two different types of MSC “licensing”: one that is cell-contact dependent and the second that is mediated by inflammatory cytokines. The varied and complex mechanisms by which MSCs can orchestrate inflammatory responses and how this function is specifically driven by inflammation support a physiological role for tissue stroma in tissue homeostasis, and it acts as a sensor of damage and initiator of tissue repair by reprogramming the inflammatory environment.
“Burnout” Coupled with Workforce Shortages Spells Trouble: Innovative Solutions Are Essential for More Satisfying Rheumatology Practice
Authors: Lenny Calabrese, Daniel F. Battafarano, Christine Stamatos, Kenneth G. Saag
Journal: Arthritis & Rheumatology (2023)

Disclosure Form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Author Correction: Astrocytes mediate long-lasting synaptic regulation of ventral tegmental area dopamine neurons
Authors: Linda Maria Requie, Marta Gómez-Gonzalo, Michele Speggiorin, Francesca Managò, Marcello Melone, Mauro Congiu, Angela Chiavegato, Annamaria Lia, Micaela Zonta, Gabriele Losi, Vanessa Jorge Henriques, Arianna Pugliese, Giada Pacinelli, Giovanni Marsicano, Francesco Papaleo, Anna Lisa Muntoni, Fiorenzo Conti, Giorgio Carmignoto
Journal: Nature Neuroscience (2023)
Review of Progress and Challenges in Bacterial Meningitis
Authors: Simone Giuliano, Francesco Sbrana, Carlo Tascini
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The Present Status of Viruses and Virus Diseases
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
CD30 co-stimulation drives differentiation of protective T cells during <i>Mycobacterium tuberculosis</i> infection
Authors: Taylor W. Foreman, Christine E. Nelson, Michelle A. Sallin, Keith D. Kauffman, Shunsuke Sakai, Francisco Otaizo-Carrasquero, Timothy G. Myers, Daniel L. Barber
Journal: The Journal of Experimental Medicine (2023)

Control of Mycobacterium tuberculosis (Mtb) infection requires generation of T cells that migrate to granulomas, complex immune structures surrounding sites of bacterial replication. Here we compared the gene expression profiles of T cells in pulmonary granulomas, bronchoalveolar lavage, and blood of Mtb-infected rhesus macaques to identify granuloma-enriched T cell genes. TNFRSF8/CD30 was among the top genes upregulated in both CD4 and CD8 T cells from granulomas. In mice, CD30 expression on CD4 T cells is required for survival of Mtb infection, and there is no major role for CD30 in protection by other cell types. Transcriptomic comparison of WT and CD30-/- CD4 T cells from the lungs of Mtb-infected mixed bone marrow chimeric mice showed that CD30 directly promotes CD4 T cell differentiation and the expression of multiple effector molecules. These results demonstrate that the CD30 co-stimulatory axis is highly upregulated on granuloma T cells and is critical for protective T cell responses against Mtb infection.
Recent Advances of Platinum‐Based Anticancer Complexes in Combinational Multimodal Therapy
Authors: Tianyuan Zhong, Jie Yu, Yong Pan, Ning Zhang, Yanxin Qi, Yubin Huang
Journal: Advanced Healthcare Materials (2023)

Abstract Platinum drugs with manifest therapeutic effects are widely used, but their systemic toxicity and the drug resistance acquired by cancer cells limit their clinical applications. Thus, the exploration on appropriate methods and strategies to overcome the limitations of traditional platinum drugs becomes extremely necessary. Combination therapy of platinum drugs can inhibit tumor growth and metastasis in an additive or synergistic manner, and can potentially reduce the systemic toxicity of platinum drugs and overcome platinum‐resistance. This review summarizes the various modalities and current progress in platinum‐based combination therapy. The synthetic strategies and therapeutic effects of some platinum‐based anticancer complexes in the combination of platinum drugs with gene editing, ROS‐based therapy, thermal therapy, immunotherapy, biological modelling, photoactivation, supramolecular self‐assembly and imaging modality are briefly described. Their potential challenges and prospects are also discussed. It is hoped that this review will inspire researchers to have more ideas for the future development of highly effective platinum‐based anti‐cancer complexes.
Trends in Buprenorphine Initiation and Retention in the United States, 2016-2022
Authors: Kao-Ping Chua, Thuy D. Nguyen, Jason Zhang, Rena M. Conti, Pooja Lagisetty, Amy S. Bohnert
Journal: JAMA (2023)

This study uses data from an all-payer database of prescriptions dispensed in US retail pharmacies to assess trends in buprenorphine initiation and retention during 2016-2022.